Dietary iron deficiency during pregnancy promotes neuroinflammation without altering brain iron levels

抄録

Iron deficiency during pregnancy is a common nutritional disorder that affects maternal brain function. Although systemic iron deficiency influences neurological function, its effects on cerebral iron homeostasis and inflammatory responses during pregnancy remain unclear. Therefore, we investigated whether dietary iron deficiency during pregnancy alters brain iron metabolism and induces neuroinflammatory responses. Female ICR mice were fed an iron-deficient or control diet before mating and throughout pregnancy. At 16 weeks of age, hematological parameters, brain iron concentrations, and expression of proteins associated with iron metabolism, oxidative stress, and inflammation were evaluated. Iron-deficient mice exhibited pronounced decreases in red blood cell count, hemoglobin concentration, and hematocrit. This was accompanied by increases in white blood cell and platelet counts, thereby confirming the induction of systemic iron deficiency. Despite these systemic changes, neither brain weight nor total brain iron concentration differed substantially between groups. In contrast, brain hemoglobin expression markedly decreased, whereas heme oxygenase-1 expression markedly increased in iron-deficient mice. This suggested altered intracellular heme and iron metabolism. Furthermore, the expression of cleaved caspase-1 and interleukin-1β was substantially increased. This indicated activation of inflammasome-associated inflammatory signaling. The stress-responsive protein DJ-1 was also markedly upregulated. This potentially reflects a compensatory response to oxidative and inflammatory stresses. Overall, maternal dietary iron deficiency promoted neuroinflammation without reducing total brain iron content. Instead, this occurred via qualitative intracellular iron handling alterations, enhanced oxidative stress, and inflammasome activation. Thus, disruption of cerebral iron homeostasis during pregnancy may represent an important mechanism linking maternal iron deficiency to brain inflammation.